Development of novel treatment for heart failure -Implication of cytokine signaling for cell therapy-

心力衰竭新疗法的开发 -细胞因子信号转导对细胞疗法的影响 -

基本信息

批准号：
15590741
负责人：
TAKIHARA Keiko
金额：
$ 2.05万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590741/
关键词：
Heart Failure Cytokine STAT3 Signal transduction Cardiac Remodeling Cardiac Myocyte Myocardial Injury Apoptosis

项目摘要

Our previous studies clearly showed that gp 130-dependent signaling pathway transduced signals directly related to cardiac myocyte survival such as induction of bcl-xL and activation of Akt. We also reported that gp 130 activation presented a protective effect on hypoxia/reoxygenation-induced cardiac myocyte damage by inducing MnSOD and scavenging ROS generation through the activation of STAT3.Transgenic mice with cardiac specific overexpression of constitutively active form of the STAT3 gene (caSTAT3-TG) exhibited increased expression of VEGF, which was accompanied by increased capillary density in the heart. These studies suggest that gp 130/STAT signaling in cardiac myocyte can control vessel growth during cardiac remodeling. We observed that the remodeling process after acute myocardial infarction was significantly attenuated and the survival rate was significantly improved in caSTAT3-TG.Recently, granulocyte-colony-stimulating factor (G-CSF) is suggested to improve heart failure after myocardial infarction. Our study demonstrated that G-CSF, through the receptor on cardiac myocytes, activates STAT3 and presents protective effect on cardiac myocytes, by using dominant negative form of STAT3 (dnSTAT3) transgenic mice. The beneficial effects of G-CSF on cardiac remodeling process was cancelled in dnSTAT3-TG. Signals through gp 130 provides new insights into the significance of cytokines in cardiac remodeling and activation of this pathway is proposed as a novel therapeutic strategy for the protection against pathophysiological stress.

我们先前的研究清楚地表明，GP 130依赖性信号通路传输信号与心肌细胞存活直接相关，例如诱导BCL-XL和AKT的激活。我们还报道说，GP 130激活对缺氧/重氧诱导的心肌细胞损害产生了保护作用，通过激活STAT3.TRANSGIC小鼠的心脏特异性过度表达STAT3 Gene（Castat3-TG）的表达增加了cap的表达，通过激活心脏特异性的心脏特异性过表达，通过激活心脏特异性的心脏特异性过表达，通过capearied capeans caperiand capeans capean capery capery caperanial capery capery capery。这些研究表明，心肌细胞中的GP 130/Stat信号传导可以控制心脏重塑期间的血管生长。我们观察到，急性心肌梗塞后的重塑过程显着减弱，并且在Castat3-TG中显着提高了生存率。建议，建议提出粒细胞 - 粘膜刺激因子（G-CSF），以改善心肌梗死后心力衰竭的心力衰竭。我们的研究表明，通过使用STAT3（DNSTAT3）转基因小鼠的显性阴性形式，通过心肌细胞上的受体激活STAT3并对心肌细胞产生保护作用。 DNSTAT3-TG取消了G-CSF对心脏重塑过程的有益影响。通过GP 130进行的信号提供了有关细胞因子在心脏重塑中的重要性的新见解，并提出了该途径的激活作为保护病理生理应激的一种新型治疗策略。

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Y.Nakaoka et al.: "Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes"Circ Res. 93. 221-229 (2003)

Y.Nakaoka 等人：“gp130 的激活通过心肌细胞中支架/对接蛋白 Gab1 与酪氨酸磷酸酶 SHP2 的相互作用来转导肥大信号”Circ Res。

DOI：
发表时间：
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影响因子：
0
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通讯作者：

K.Yamauchi-Takihara et al.: "Kluwer Academic Publishers"A novel role for cytokine signaling in cardiac remodeling. In : Cardiac Remodeling and Failure. 350 (2003)

K.Yamauchi-Takihara 等人：“Kluwer 学术出版社”细胞因子信号传导在心脏重塑中的新作用。

DOI：
发表时间：
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影响因子：
0
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通讯作者：

Activation of gp 130 transducer hypertropic signal through interaction of scaffolding docking protein Gab1 with tyrosie phosphatase SHP2 in cardiomyocytes.

通过支架对接蛋白 Gab1 与心肌细胞中酪氨酸磷酸酶 SHP2 的相互作用激活 gp 130 传感器肥大信号。

DOI：
发表时间：
2003
期刊：
Circ Res 93
影响因子：
0
作者：
Y.Nakaoka;K.Nishida;Y.Fujio;M.Izumi;K.Terai;Y.Oshima;S.Sugiyama;S.Matsuda;S.Koyasu;K.Yamauchi-Takihara;T.Hirano;I.Kawase;H.Hirota.
通讯作者：
H.Hirota.

Activation of gp130 transduces hypertropic signal through interaction of scaffolding/docking protein Gab1 with tyrosie phosphatase SHP2 in cardiomyocytes.

gp130 的激活通过支架/对接蛋白 Gab1 与心肌细胞中酪氨酸磷酸酶 SHP2 的相互作用来转导肥厚信号。